Impact of instantaneous wave-free ratio on graft failure after coronary artery bypass graft surgery.

BACKGROUND: We aimed to assess an impact of instantaneous wave-free ratio (iFR) on a graft failure after coronary artery bypass grafting (CABG). METHODS AND RESULTS: A total of 131 coronary arteries from 88 patients who underwent invasive coronary angiography, intracoronary pressure measurements, CABG, and scheduled follow-up coronary computed tomography angiography within one year were investigated. All studied arteries had FFR <0.80. The rate of graft failure was significantly higher in vessels with negative iFR (>0.89) than in those with positive iFR (<0.89) (25.7% vs. 7.3%, p = 0.012). The graft failure rates increased as the preoperative iFR values rose (iFR <0.80, 3.3%; iFR: 0.80-0.84, 5.6%; iFR: 0.85-0.89, 16.0%; iFR: 0.90-0.94, 28.0%; and iFR: 0.95-1.00, 50.0%; p = 0.002). A cut-off value of iFR to predict graft failures was determined as 0.84 by receiver-operating characteristic curve analysis with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 88%, 62%, 25%, 97%, and 66%, respectively. CONCLUSIONS: The risk of graft failure becomes higher, as the preoperative iFR increases. The graft failure is significantly more frequent when a bypass graft is anastomosed on vessels with negative iFR than those with positive iFR.

Noninvasive assessment of left ventricular end-diastolic pressure by deceleration time of early diastolic mitral annular velocity in patients with heart failure.

OBJECTIVE: To examine the diagnostic ability of the deceleration time of early mitral annular velocity (e'DT) as determined by tissue Doppler velocity image, a method for assessing LV filling pressure. BACKGROUNDS: Estimation of LV filling pressure by Doppler echocardiography requires a combination of various parameters. Therefore, there remains a need for a simple index in LV filling pressure estimation. The e' is known to be reduced and delayed with increased LV filling pressure during development of heart failure. Thus, we hypothesized that e'DT would be shortened as LV filling pressure is increased. METHODS: Simultaneous LV end-diastolic pressure (LVEDP) measurement and Doppler echocardiography were performed in 94 patients who were admitted to our hospital for heart failure. Exclusion criteria were atrial fibrillation, mitral valve surgery, and acute coronary syndrome. RESULTS: The e'DT in 31 patients with LVEDP >16 mm Hg (68±13 ms) was significantly shorter than that in 63 patients with LVEDP ≤16 mm Hg (103±27 ms). Both e'DT and early transmitral flow velocity (E)/e' were significantly correlated with LVEDP. In 30 patients with 10-14 E/e', significance of correlation in e'DT was remained, while E/e' was not. The area under the ROC curve for prediction of LVEDP >16 mm Hg for e'DT was greater than that for E/e' (0.91 vs 0.74, P=.046). CONCLUSION: The e'DT is useful to assess LV filling pressure, especially in 10-14 E/e'. This simple tissue Doppler index may be a potential parameter for easily distinguishing between mild and severe heart failures.

Effects of intravenous bolus injection of nicorandil on renal artery flow velocity assessed by color Doppler ultrasound.

BACKGROUND: Previous animal studies have shown that a potassium channel opener, nicorandil, provokes vasodilation in renal microvasculature and increases renal blood flow. We conducted a clinical study that aimed to evaluate the effect of nicorandil on renal artery blood flow in comparison with nitroglycerin by using color Doppler ultrasound. METHODS: The present study enrolled 40 patients with stable coronary artery disease who had no renal arterial stenosis and renal parenchymal disease. The patients received intravenous administration of nicorandil (n=20) or nitroglycerin (n=20). Before and after the administration, renal artery blood flow velocity was measured by color-guided pulsed-wave Doppler. RESULTS: The peak-systolic, end-diastolic, and mean renal artery blood flow velocities before the administration were not different between the nicorandil group and the nitroglycerin group. The peak-systolic (79±15cm/s to 99±21cm/s, p<0.001; and 78±19cm/s to 85±19cm/s, p=0.004), end-diastolic (22±5cm/s to 28±8cm/s, p<0.001; and 24±6cm/s to 26±6cm/s, p=0.005) and mean (41±6cm/s to 49±9cm/s, p<0.001; and 43±9cm/s to 45±9cm/s, p=0.009) renal artery flow velocities increased significantly in either group. The nominal changes in the peak-systolic (20±10cm/s vs. 7±8cm/s, p<0.001), end-diastolic (5±4cm/s vs. 2±3cm/s, p=0.001), and mean (8±5cm/s vs. 2±2cm/s, p<0.001) renal artery blood flow velocities were significantly greater in the nicorandil group compared with the nitroglycerin group. CONCLUSION: Intravenous nicorandil increased renal artery blood flow velocity in comparison with nitroglycerin. Nicorandil has a significant effect on renal hemodynamics.

Impact of functional focal versus diffuse coronary artery disease on bypass graft patency.

BACKGROUND: Pressure guidewire pullback recording can differentiate between functional focal and diffuse disease types in coronary artery disease. The aim of this study was to compare the outcome of coronary artery bypass graft (CABG) patency between patients with functional focal versus diffuse disease types in recipient coronary arteries. METHODS AND RESULTS: We investigated 89 patients who underwent pressure guidewire pullback in the left anterior descending (LAD) artery before CABG using internal mammary artery (IMA). Based on the pressure guidewire pullback data, the LAD lesions were classified into functional focal disease (abrupt pressure step-up; n=58) or functional diffuse disease (gradual pressure increase; n=31). Follow-up computed tomography (CT) angiography was conducted within 1year after CABG to assess the bypass graft patency. Pre CABG, LAD angiographic percent diameter stenosis (57±10% vs. 54±12%, p=0.228) and fractional flow reserve (FFR) (0.68±0.07 vs. 0.69±0.07, p=0.244) were not different between the functional focal and diffuse disease groups. The CABG procedure characteristics were similarly comparable between the two groups. In the follow-up CT angiography after CABG, occlusion or string sign of the IMA graft to LAD was more frequently observed in the functional diffuse disease group than in the functional focal disease group (26% vs. 7%, p=0.021). CONCLUSION: In CABG, functional diffuse disease in the recipient coronary artery was associated with an increased risk of the graft failure in comparison with functional focal disease.

Long-term outcome after deferral of revascularization in patients with intermediate coronary stenosis and gray-zone fractional flow reserve.

BACKGROUND: A strategy of deferred percutaneous coronary intervention for coronary stenosis with fractional flow reserve (FFR) 0.75-0.80, termed the gray zone, remains a matter of debate. The aim of this study was to assess the safety of deferring revascularization for patients with FFR 0.75-0.80 compared with those with FFR >0.80. METHODS AND RESULTS: We assessed 3-year clinical outcome in 150 patients with angiographically intermediate stenosis who had revascularization deferred on the basis of FFR ≥ 0.75 (FFR 0.75-0.80, n=56; FFR >0.80, n=94). Target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction (MI), and ischemia-driven target vessel revascularization (TVR) was evaluated during follow-up. Cardiac death was observed in 1 patient with FFR 0.75-0.80. There was no target vessel-related MI in either group. The incidence of ischemia-driven TVR was higher in patients with FFR 0.75-0.80 than in those with FFR >0.80 (14% vs. 3%, P=0.020). TVF-free survival was significantly worse for the patients with FFR 0.75-0.80 than those with FFR >0.80 (hazard ratio, 5.2; 95% confidence intervals: 1.4-19.5; P=0.015). CONCLUSIONS: Patients with FFR 0.75-0.80 were at higher risk of TVF mainly due to TVR than those with FFR >0.80.

Effect of atorvastatin therapy on fibrous cap thickness in coronary atherosclerotic plaque as assessed by optical coherence tomography: the EASY-FIT study.

BACKGROUND: The detailed mechanism of plaque stabilization by statin therapy is not fully understood. OBJECTIVES: The aim of this study was to assess the effect of lipid-lowering therapy with 20 mg/day of atorvastatin versus 5 mg/day of atorvastatin on fibrous cap thickness in coronary atherosclerotic plaques by using optical coherence tomography (OCT). METHODS: Seventy patients with unstable angina pectoris and untreated dyslipidemia were randomized to either 20 mg/day or 5 mg/day of atorvastatin therapy. OCT was performed to assess intermediate nonculprit lesions at baseline and 12-month follow-up. RESULTS: Serum low-density lipoprotein cholesterol level was significantly lower during therapy with 20 mg/day compared with 5 mg/day of atorvastatin (69 mg/dl vs. 78 mg/dl; p = 0.039). The increase in fibrous cap thickness was significantly greater with 20 mg/day compared with 5 mg/day of atorvastatin (69% vs. 17%; p < 0.001). The increase in fibrous cap thickness correlated with the decrease in serum levels of low-density lipoprotein cholesterol (R = -0.450; p < 0.001), malondialdehyde-modified low-density lipoprotein (R = -0.283; p = 0.029), high-sensitivity C-reactive protein (R = -0.276; p = 0.033), and matrix metalloproteinase-9 (R = -0.502; p < 0.001), and the decrease in grade of OCT-derived macrophages (R = -0.415; p = 0.003). CONCLUSIONS: Atorvastatin therapy at 20 mg/day provided a greater increase in fibrous cap thickness in coronary plaques compared with 5 mg/day of atorvastatin. The increase of fibrous cap was associated with the decrease in serum atherogenic lipoproteins and inflammatory biomarkers during atorvastatin therapy. (Effect of Atorvastatin Therapy on Fibrous Cap Thickness in Coronary Atherosclerotic Plaque as Assessed by Optical Coherence Tomography: The EASY-FIT Study; NCT00700037).

Coronary endothelial dysfunction is associated with inflammation and vasa vasorum proliferation in patients with early atherosclerosis.

OBJECTIVE: Endothelial dysfunction is an early manifestation of atherosclerosis. Inflammation and vasa vasorum play a pivotal role in the pathophysiology of plaque initiation, development, and complications. Optical coherence tomography allows high-resolution imaging of tissue microstructure. Therefore, the aim of this study was to test the hypothesis that segments with endothelial dysfunction show macrophages and vasa vasorum in patients with early coronary artery disease. APPROACH AND RESULTS: Optical coherence tomography images were obtained from 40 patients with mild coronary atherosclerosis who underwent coronary endothelial function assessment. Optical coherence tomography findings, including macrophages and microchannels, were evaluated in 76 coronary segments corresponding to those in endothelial response to acetylcholine. Coronary artery diameter change in response to acetylcholine was more severe in segments showing macrophages (-17.7±14.7% versus -6.3±13.9%; P<0.01) and microchannels (-15.9±15.9% versus -6.4±13.5%; P<0.01) than those without. There were increasing trends of the prevalence of macrophages and microchannels with endothelial dysfunction as stratified by quartiles of coronary artery diameter change (P<0.01 and P=0.02 for trend, respectively). In particular, segments with both macrophages and microchannels (n=12) tended to have worse endothelial function than those with macrophages alone (n=15) and microchannels alone (n=15; -22.1±14.6% versus -10.9±15.6% and -10.9±15.6%; P=0.07 and P=0.06, respectively). CONCLUSIONS: Epicardial endothelial dysfunction was associated with optical coherence tomography -identified macrophages and microchannels in mild coronary atherosclerosis. The current study further supports the role of inflammation and vasa vasorum proliferation in the early stage of coronary atherosclerosis.

Ischemic cardiomyopathy is associated with coronary plaque progression and higher event rate in patients after cardiac transplantation.

BACKGROUND: Cardiac allograft vasculopathy is the leading cause of graft failure and death in heart transplant (HTx) recipients; however, the association between the etiology of heart failure (ischemic cardiomyopathy [ICM] or non-ICM) that led to HTx and progression of cardiac allograft vasculopathy, and adverse events after HTx has not been explored. METHODS AND RESULTS: We retrospectively included 165 HTx patients, who were followed-up with at least 2 virtual histology-intravascular ultrasound examinations after HTx, and grouped them as ICM (n=46) or non-ICM (n=119). Coronary artery plaque volume was analyzed using virtual histology-intravascular ultrasound, and cardiovascular event data-a composite of myocardial infarction, hospitalization for heart failure and arrhythmia, revascularization, retransplantation, and death including cardiovascular death-were collected from the medical records of all study subjects. ICM patients had significantly higher plaque volume at both first (P=0.040) and follow-up (P=0.015) intravascular ultrasound examinations. After multivariate adjustment for traditional coronary risk factors, ICM was significantly associated with plaque progression (odds ratio 3.10; CI 1.17 to 9.36; P=0.023). Ten-year cardiovascular event-free survival was 50% in ICM patients compared with 84% in non-ICM patients (log-rank test P=0.003). In multivariate Cox proportional hazard analysis, ICM was significantly associated with a higher event rate after HTx (hazard ratio 2.02; 95% CI 1.01 to 4.00; P=0.048). CONCLUSION: Our study demonstrates that ischemic etiology of cardiomyopathy prior to HTx may be independently associated with plaque progression and higher event rate after HTx.

High-sensitivity C-reactive protein and plaque composition in patients with stable angina pectoris: a virtual histology intravascular ultrasound study.

OBJECTIVE: Elevated high-sensitivity C-reactive protein (hs-CRP) is related to clinical outcome in coronary artery disease. We used virtual histology intravascular ultrasound to evaluate the relationship between serum hs-CRP level and coronary plaque composition in patients with stable angina pectoris. METHODS AND RESULTS: Overall 113 consecutive patients with stable angina pectoris who had a de-novo culprit lesion were examined in this study. Patients were divided into an elevated hs-CRP group (>3 mg/l; n=40) or a normal hs-CRP group (n=73). Grayscale and virtual histology intravascular ultrasound analysis was performed across the entire culprit lesion. Mean plaque area was similar in both groups. Lesion length (18+/-5 vs. 16+/-6 mm, P<0.046) was significantly greater in the elevated hs-CRP group than that in the normal hs-CRP group. Although the percentage of dense calcium, fibrofatty tissue, and fibrous tissue was not different between the two groups, the percentage of necrotic core was significantly greater in the elevated hs-CRP group compared with the normal hs-CRP group (20+/-9 vs. 16+/-8%, P=0.014). The percentage of necrotic core was positively correlated with the serum hs-CRP level (r=0.20, P=0.037). A multivariate logistic regression model showed that the percentage of necrotic core was associated with elevated hs-CRP (P=0.019; odds ratio=1.1; 95% confidence interval=1.01-1.12). CONCLUSION: Elevated hs-CRP was related to the amount of necrotic core in the culprit lesion of stable angina pectoris. Our results suggest that elevated hs-CRP might reflect the inflammatory activity of the coronary atherosclerotic plaque even in the setting of stable angina pectoris.

Implication of plaque color classification for assessing plaque vulnerability: a coronary angioscopy and optical coherence tomography investigation.

OBJECTIVES: The purpose of this study was to assess the relationship between plaque color evaluated by coronary angioscopy and fibrous cap thickness estimated by optical coherence tomography (OCT) in vivo. BACKGROUND: Yellow color intensity of coronary plaque evaluated by coronary angioscopy might be associated with plaque vulnerability. METHODS: Seventy-seven coronary artery plaques in patients with acute coronary syndrome were observed by angioscopy and OCT. Plaque color was graded as white, light yellow, yellow, or intensive yellow. RESULTS: There were significant differences among the groups classified by plaque color with respect to the fibrous cap thickness estimated by OCT: 389 +/- 74 mum in white plaques, 228 +/- 51 microm in light yellow plaques, 115 +/- 28 microm in yellow plaques, and 59 +/- 14 microm in intensive yellow plaques (p < 0.0001). In Spearman rank-order correlation analysis, there was a significant negative correlation between yellow color intensity and fibrous cap thickness (p < 0.0001). Furthermore, 80% of intensive yellow plaques were thin cap fibroatheroma with a cap thickness of < or =65 microm. CONCLUSIONS: The plaque color in coronary angioscopy was determined by the fibrous cap thickness, which was assessed by OCT. Although coronary angioscopy remains a specialized research tool, it might allow us to evaluate plaque vulnerability.

Assessment of culprit lesion morphology in acute myocardial infarction: ability of optical coherence tomography compared with intravascular ultrasound and coronary angioscopy.

OBJECTIVES: The aim of the present study was to evaluate the ability of optical coherence tomography (OCT) for assessment of the culprit lesion morphology in acute myocardial infarction (AMI) in comparison with intravascular ultrasound (IVUS) and coronary angioscopy (CAS). BACKGROUND: Optical coherence tomography is a new intravascular imaging method with a high resolution of approximately 10 microm. This may allow us to assess the vulnerable plaques in detail in vivo. METHODS: We enrolled 30 patients with AMI, and analyzed the culprit lesion by OCT, CAS, and IVUS. RESULTS: The average duration from the onset of symptom to OCT imaging was 3.8 +/- 1.0 h. The incidence of plaque rupture observed by OCT was 73%, and it was significantly higher than that by CAS (47%, p = 0.035) and IVUS (40%, p = 0.009). Furthermore, OCT (23%) was superior to CAS (3%, p = 0.022) and IVUS (0%, p = 0.005) in the detection of fibrous cap erosion. The intracoronary thrombus was observed in all cases by OCT and CAS, but it was identified in 33% by IVUS (vs. OCT, p < 0.001). Only OCT could estimate the fibrous cap thickness, and it was 49 +/- 21 microm. The incidence of thin cap fibroatheroma (TCFA) was 83% in this population by OCT. CONCLUSIONS: Optical coherence tomography is a feasible imaging modality in patients with AMI and allows us to identify not only plaque rupture, but also fibrous cap erosion, intracoronary thrombus, and TCFA in vivo more frequently compared with conventional imaging techniques.

The effect of senescence of endothelial progenitor cells on in-stent restenosis in patients undergoing coronary stenting.

OBJECTIVE: Restenosis after stent implantation is caused by endothelial cell damage and subsequent neointimal formation. The objective of this study is to elucidate the relevance of endothelial progenitor cells (EPCs) in the development of in-stent restenosis in patients undergoing stent implantation. PATIENTS OR MATERIALS: The subjects were 46 patients who underwent coronary stenting. Blood samples were collected at the time of follow-up coronary angiography after coronary stenting. EPCs were isolated from blood samples and cultured. Their phenotypes were confirmed by uptake of acetylated low-density lipoprotein and binding of fluorescein isothiocyanate-labeled Ulex europaeus agglutinin 1 lectin. The number of colony-forming units (CFUs) and the senescent cells, determined by acidic beta-galactosidase staining, was counted. Angiogenic growth factors secreted by EPCs, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), hepatocyte growth factor (HGF), and macrophage chemoattractant protein (MCP-1) from the culture medium were also measured by enzyme-linked immunosorbent assay. RESULTS: Patients with in-stent restenosis (defined as >40% stenosis, n=16) had a decreased number of CFUs (p<0.05), and increased senescent cells (p<0.05), compared to patients without restenosis (n=30). There was no significant difference of angiogenic growth factors (VEGF, HGF, b-FGF, and MCP-1) secreted by EPCs between the two groups. On multivariate analysis, an increased number of senescent EPCs was the indepen-dent factor associated with in-stent restenosis (OR 1.10, 95% CI 1.01 to 1.20). CONCLUSION: These data suggested that EPCs might be involved in the development of in-stent restenosis.

Oxidized low-density lipoprotein inhibits vascular endothelial growth factor-induced endothelial progenitor cell differentiation.

1. Bone marrow-derived endothelial progenitor cells (EPC) in the peripheral blood of adult animals and humans have been shown to be incorporated into neovascularization. In contrast, hypercholesterolaemia impairs angiogenesis and collateral vessel formation in response to regional tissue ischaemia. We investigated whether oxidized LDL (oxLDL) affected human EPC differentiation. 2. When isolated human mononuclear cells (MNC) were incubated with vascular endothelial growth factor (VEGF), the number of differentiated, adherent EPC, as assessed by an in vitro culture assay, was increased in a dose-dependent manner (P < 0.01). When MNC were incubated with oxLDL at 1, 5 and 10 microg/mL in the presence of 100 ng/mL VEGF for 24 h, oxLDL dose-dependently reduced the number of differentiated, adherent EPC. 3. Vascular endothelial growth factor-induced EPC differentiation was significantly inhibited by pharmacological phosphatidylinositol 3-kinase blockers (either 10 nmol/L wortmannin or 10 micromol/L LY294002). Interestingly, immunoblotting analysis revealed that oxLDL dose-dependently led to dephosphorylation and, thus, deactivation of Akt in the presence of VEGF. Finally, these inhibitory effects induced by oxLDL were abolished by pretreatment with 1 micromol/L atorvastatin (P < 0.01). 4. Our data indicate that oxLDL inhibits VEGF-induced EPC differentiation through the dephosphorylation of Akt.